eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Genetics

Thanatophoric Dysplasia: Differential Diagnoses & Workup

Author: Germaine L Defendi, MD, MS, FAAP, Associate Clinical Professor, Department of Pediatrics, Olive View-UCLA Medical Center
Contributor Information and Disclosures

Updated: Nov 6, 2009

Differential Diagnoses

Achondrogenesis
Achondroplasia
Asphyxiating Thoracic Dystrophy (Jeune Syndrome)
Hypophosphatasia
Osteogenesis Imperfecta

Other Problems to Be Considered

Achondroplasia (homozygous form)
Camptomelic dysplasia (CD)
Congenital hypophosphatasia
Dyssegmental dysplasia, Silverman-Handmaker type (DDSH)
Osteogenesis Imperfecta (OI), type II 
Platyspondylic lethal skeletal dysplasia (PLSD)
Rhizomelic chondrodysplasia punctata (RCDP)
Severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN)
Short rib-polydactyly syndromes

Workup

Laboratory Studies

The following studies are indicated in suspected cases of thanatophoric dysplasia (TD):

  • Chromosome analysis
  • Molecular testing for FGFR3 with targeted and sequence mutation analyses available

Imaging Studies

  • Prenatal ultrasonography2
    • Two-dimensional (2D) ultrasonography reveals polyhydramnios, growth deficiency, ventriculomegaly, micromelia, a narrow thorax, and flattened vertebrae.
    • Three-dimensional (3D) ultrasonography may reveal the fetal face, scapular anomalies, and chest hypoplasia better than 2D ultrasonography.
  • Postnatal radiographs and other imaging studies (CT, MRI) reveal the following:
    • Rhizomelic shortening and irregular metaphyses of the long bones and "telephone receiver–shaped" bowed femurs
    • Flattened vertebral bodies (platyspondyly) with wide intervertebral spacing
    • Enlarged skull and a small foramen magnum with potential evidence of brain stem compression
    • CNS abnormalities such as hydrocephalus, brainstem hypoplasia, temporal lobe malformations, neuronal migration abnormalities

Histologic Findings

  • Histologic evaluation of long bone structure in thanatophoric dysplasia shows disruption of endochondral ossification but not of periosteal ossification.

More on Thanatophoric Dysplasia

Overview: Thanatophoric Dysplasia
Differential Diagnoses & Workup: Thanatophoric Dysplasia
Treatment & Medication: Thanatophoric Dysplasia
Follow-up: Thanatophoric Dysplasia
Multimedia: Thanatophoric Dysplasia
References
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References

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  2. [Guideline] Cunniff C. Prenatal screening and diagnosis for pediatricians. Pediatrics. Sep 2004;114(3):889-94. [Medline].

  3. Baker KM, Olson DS, Harding CO, Pauli RM. Long-term survival in typical thanatophoric dysplasia type 1. Am J Med Genet. Jun 27 1997;70(4):427-36. [Medline].

  4. Chen CP, Chern SR, Wang W, Wang TY. Second-trimester molecular diagnosis of a heterozygous 742 --> T (R248C) mutation in the FGFR3 gene in a thanatophoric dysplasia variant following suspicious ultrasound findings. Ultrasound Obstet Gynecol. Mar 2001;17(3):272-3. [Medline].

  5. Delezoide AL, Lasselin-Benoist C, Legeai-Mallet L, et al. Abnormal FGFR 3 expression in cartilage of thanatophoric dysplasia fetuses. Hum Mol Genet. Oct 1997;6(11):1899-906. [Medline].

  6. Garjian KV, Pretorius DH, Budorick NE, et al. Fetal skeletal dysplasia: three-dimensional US--initial experience. Radiology. Mar 2000;214(3):717-23. [Medline].

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  8. Karczeski B, Cutting GR. Thanatophoric Dysplasia. GeneReviews. Available at http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=td. Accessed September 1, 2009.

  9. Kolble N, Sobetzko D, Ersch J. Diagnosis of skeletal dysplasia by multidisciplinary assessment: a report of two cases of thanatophoric dysplasia. Ultrasound Obstet Gynecol. Jan 2002;19(1):92-8. [Medline].

  10. Lemyre E, Azouz EM, Teebi AS, et al. Bone dysplasia series. Achondroplasia, hypochondroplasia and thanatophoric dysplasia: review and update. Can Assoc Radiol J. Jun 1999;50(3):185-97. [Medline].

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  14. Rousseau F, el Ghouzzi V, Delezoide AL, et al. Missense FGFR3 mutations create cysteine residues in thanatophoric dwarfism type I (TD1). Hum Mol Genet. Apr 1996;5(4):509-12. [Medline].

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  21. Thanatophoric Dysplasia, Type II; TD2. Online Mendelian Inheritance in Man. Available at http://www.ncbi.nlm.nih.gov. Accessed September 1, 2009.

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  24. Weber M, Johannisson T, Thomsen M, et al. Thanatophoric dysplasia type I: new radiologic, morphologic, and histologic aspects toward the exact definition of the disorder. J Pediatr Orthop B. Jan 1998;7(1):1-9. [Medline].

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Further Reading

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Keywords

thanatophoric dysplasia, TD, skeletal dysplasia, thanatophoric dwarfism, fatal skeletal dysplasia, short limb dwarfism, TD type I, TD type 1, TDI, TD1, TD type II, TD type 2, TDII, TD2

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Contributor Information and Disclosures

Author

Germaine L Defendi, MD, MS, FAAP, Associate Clinical Professor, Department of Pediatrics, Olive View-UCLA Medical Center
Germaine L Defendi, MD, MS, FAAP is a member of the following medical societies: Ambulatory Pediatric Association and American Academy of Pediatrics
Disclosure: Nothing to disclose.

Medical Editor

Ian Krantz, MD, Department of Pediatrics, Assistant Professor, University of Pennsylvania and Children's Hospital of Philadelphia
Ian Krantz, MD is a member of the following medical societies: American Society of Human Genetics
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Robert Anthony Saul, MD, Clinical Professor, Department of Pediatrics, University of South Carolina; Senior Clinical Geneticist, Greenwood Genetic Center
Robert Anthony Saul, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics, and American College of Physician Executives
Disclosure: Nothing to disclose.

CME Editor

Paul D Petry, DO, FACOP, FAAP, Consulting Staff, Freeman Pediatric Care, Freeman Health System
Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association
Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD, Professor, Department of Pediatrics, Pathology and Microbiology, Executive Director, Hattie B Munroe Center for Human Genetics, University of Nebraska Medical Center
Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association
Disclosure: Nothing to disclose.

 
 
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